Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study, a phase III multicenter randomized trial opened by ECOG in April 1983 and closed in June 1986 was designed to evaluate whether a combination of doxorubicin and an intravenous formulation of diethylstilbestrol diphosphate (DES) was superior to doxorubicin alone in men with hormone refractory prostate cancer. All patients received doxorubicin at a dose of 50 mg/m2 iv every 3 wk either alone or with 1 g DES iv daily for 5 d followed by 1 g iv twice weekly for four cycles (12 wk). The 51 evaluable patients with visceral metastases displayed a significantly increased response rate (27% vs 63%) on the combined therapy arm (p = 0.04). However, the 111 evaluable patients with osseous disease exhibited no difference in response rate between either arm with a p-value of >0.99. Similarly, clinical response rates revealed no difference between the two arms. Cases of cardiac toxicity graded as severe, life threatening, or lethal in the combined therapy arm were 10 times more frequent in the combined-therapy arm than in the doxorubicin-alone group (6.75% compared to 0.7%). This difference was statistically significant (p = 0.0041). All of the cases of superficial and deep venous thrombosis occurred on the combined-therapy arm. There were no other significant differences in the numbers of grade 3 or 4 toxic events. The most common toxicity was hematologic. Failure-free survival duration did reach statistical significance in the combined-therapy group (p = 0.012), although the actual durations were short (2.6-3.2 mo). There was no difference in overall survival between the two groups.
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PMID:Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882): an Eastern Cooperative Oncology Group study. 1283 16

Hormone-refractory prostate cancer (HRPC) encompasses a wide spectrum of patients, including patients with prostate-specific antigen (PSA)--only disease, those with increasing PSA levels yet stable metastatic disease, and those with increasing PSA levels and objective evidence of progressive metastases. Unfortunately, with the historical lack of effective therapy in this population, the oncologist is faced with few data with which to make difficult clinical decisions. Although our understanding of the biology of androgen independence continues to improve, and our fund of potential therapeutic agents has widened, multiple trial-specific and patient-specific obstacles have contributed to the difficulty in demonstrating clear benefit to therapy. Herein, we will review the biology of androgen-independent prostate cancer, the historical impediments to clinical trials in this population, and the reasons to treat, or not to treat, the patient with HRPC.
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PMID:The patient with hormone-refractory prostate cancer: determining who, when, and how to treat. 1474 51

Whether definitive radiotherapy (RT) is still an option for patients with clinically prostate-confined prostate cancer treated with androgen deprivation (AD) alone who develop a rising prostate-specific antigen (PSA) is not clear. In this retrospective series, we report the outcome of 29 such patients treated with "curative" radiotherapy at our institution between 1991 and 2000. At initial diagnosis, all patients had evidence of prostate-confined disease and for several reasons underwent AD alone. Afterward all patients developed rising PSA, but again, without clinical evidence of distant/pelvic node disease. All underwent RT with curative intent up to 70 Gy (66 to 76 Gy). Median follow-up after radiotherapy is 33.1 month (range: 7-134.2 months). For living patients, minimum and median follow-ups are 30.4 and 55.4 months, respectively. Twenty-three patients (79%) developed overt clinical disease, most of which (19/23, 83%) involved distant sites, whereas isolated locoregional failure was observed in only 4 patients (4/23, 17%). The estimates of locoregional control rate (LRC), actuarial incidence of distant metastases, and overall survival at 5 years are 89 +/- 7%, 68 +/- 9%, and 28 +/- 9%, respectively. Although we were unable to find any predictor of LRC at univariate analysis, patients with low Gleason score at diagnosis, lower PSA at RT, lower risk category and advanced age were less likely to develop distant disease. RT has a palliative role, because most patients with still presumed localized hormone refractory prostate cancer will develop distant metastases. A subset of patients, those with more differentiated tumor at diagnosis and with pre-RT PSA less than 20 ng/mL, might be considered for a more aggressive locoregional approach.
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PMID:Is there a "curative" role of radiotherapy for clinically localized hormone refractory prostate cancer? 1517 Jan 45

Prostate cancer is the second most common cancer affecting men in Europe and the USA. The incidence of prostate cancer has risen by 60-75% in the Western world in the last 15 years. One in twelve men over the age of 60 develop prostate cancer and this figure is expected to rise to three in twelve in the next 20 years. Early prostate cancer often does not cause symptoms. However, patients may present with lower urinary tract symptoms (LUTS) and therefore, such patients should be investigated. Effective treatment in the form of surgery and radiotherapy is availabLe for individuals with localised disease, and the effectiveness of different combination therapy is being assessed to improve the outcome further. Approximately 20% of the patients have metastatic disease on presentation. The mainstay of treatment for these patients is androgen ablation therapy; however patients on this regime eventually relapse and develop an androgen independent tumour. This aggressive stage of the disease carries a high morbidity and mortality. At present the treatment for such hormone refractory prostate cancer is inadequate and the desperate search for alternative forms of therapy continues.
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PMID:Understanding prostate cancer. 1592 Sep 15

Prostate cancer is the second most common cancer in men in the UK, and the incidence of prostate cancer has increased dramatically over the past two decades. Although most men are diagnosed at early stage, more than 50% develop locally advanced or metastatic disease. Androgen ablation with luteinising hormone-releasing hormone (LHRH) agonists alone, or in combination with anti-androgens, is the standard treatment for men with metastatic prostate cancer. Unfortunately, almost all men develop progressive disease after a variable time period, despite the maximal androgen blockade. The management of hormone refractory prostate cancer (HRPC) is challenging, as there is no uniformly accepted strategy. Various treatment options, including second-line hormone therapy, are discussed. Chemotherapy is being increasingly used and, importantly, docetaxel and estramustine may play an important role in the near future. The role of radiotherapy, strontium-89, bisphosphonates, novel agents and future therapies are also outlined.
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PMID:Management of patients with hormone refractory prostate cancer. 1563 Aug 42

Metastases from prostate cancer to the brain are very unusual and are seldom reported in the clinical literature. We report 2 cases of advanced stage prostate cancer with intracranial metastasis. One patient developed intracranial metastasis 5 years after step-up treatment. He had hormone refractory prostate cancer with a high level of prostate specific antigen (PSA). Unfortunately, he died of sepsis 3 weeks after craniotomy. The other patient with various neurologic symptoms and a normal PSA level responded to hormone therapy well. He had an uneventful postoperative course and has survived for more than 21 months after surgery. We also reviewed the literature and suggest that aggressive treatment, including neurosurgery, could improve the survival of certain patients with advanced prostate cancer with intracranial metastasis.
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PMID:Intracranial metastasis of prostate cancer: report of two cases. 1564 1

The diagnosis and management of prostate cancer is hampered by the absence of markers capable of identifying patients with metastatic disease. In order to identify potential new markers for prostate cancer, we compared gene expression signatures of matched androgen-dependent and hormone refractory prostate cancer xenografts. One candidate gene overexpressed in a hormone refractory xenograft was homologous to the regenerating protein gene family, a group of secreted proteins expressed in the gastrointestinal tract and overexpressed in inflammatory bowel disease and cancer. This gene, Reg IV, was confirmed to be differentially expressed in the LAPC-9 hormone refractory xenograft. Consistent with its up-regulation in a hormone refractory xenograft, it is expressed in several prostate tumors after neoadjuvant hormone ablation therapy. As predicted by its sequence homology, it is secreted from transiently transfected cells. It is also expressed strongly in a majority of hormone refractory metastases represented on two high-density tissue microarrays. In comparison, it is not expressed by any normal prostate specimens and only at low levels in approximately 40% of primary tumors. These data support Reg IV as a candidate marker for hormone refractory metastatic prostate cancer.
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PMID:Reg IV: a promising marker of hormone refractory metastatic prostate cancer. 1578 72

Hormone refractory prostate cancer is dominated by osseous metastases. Bisphosphonates are able to reduce bone resorption. Sixteen hormone refractory prostate cancer patients with related bone metastases were included in the study. Group A consisted of patients who were not treated with bisphosphonates (n=9) and group B consisted of patients who had received bisphosphonates treatment previously, but not receiving currently (n=7). All patients were treated with the same analgesic medications. Clodronate 400 mg; 1200 mg/day (p.o.) was added to the treatment of the patients in group A. Visual Analogue Scale (VAS) scores, consumptions and side effects of analgesics were recorded by two week intervals. Alkaline phosphatase, creatinine and serum Ca++ levels were controlled by 4 week intervals. At the end of the 12th week, the study was ended. In Group A, VAS decreased at the end of the 2nd week but in Group B VAS decreased in the 4th week. VAS decreased 75% in group A and 65.7% in group B and the difference was considered statistically significant (p<0.0001). Clodronate treatment was stopped in 2 patients because of nausea, 7 patients are still being treated with clodronate. We conclude that bisphosphonates treatment of painful osseous metastasis due to hormone refractory prostate cancer results in significant pain decrease.
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PMID:[The effects of clodronate for the pain treatment of bone metastasis due to prostate cancer]. 1579 1

The development of resistance to anti-cancer therapies in bones is a major hurdle preventing long-lasting clinical responses to anti-cancer therapies in hormone refractory prostate cancer. Herein, we present the major signal transduction pathways, which are activated in prostate cancer cells residing at bone metastasis microenvironment. These intracellular signal transduction pathways can inhibit anti-cancer therapy-induced apoptosis of metastatic prostate cancer cells, thereby optimizing their survival, locally. Employment of this knowledge in a clinical setting provides the conceptual framework for the development of bone-targeted therapies for advanced prostate cancer. Indeed, bone metastasis microenvironment-targeted therapies illustrate a novel paradigm in cancer treatment: anti-tumor treatment strategies may not only aim at directly inducing cancer cell apoptosis, but can also target the tumor metastasis microenvironment, and neutralize the protection it confers on metastatic cancer cells.
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PMID:Prostate cancer cell survival pathways activated by bone metastasis microenvironment. 1595 29

Hormone-refractory prostate cancer (HRCaP) is both heterogeneous and lethal. Multiple treatment options exist, including secondary hormonal manipulations, chemotherapy, experimental options, and best supportive care. Choosing the appropriate therapy for an individual patient depends on several important clinical factors such as the presence or absence of symptomatic metastatic disease, age and comorbidities, and prostate-specific antigen velocity. While only docetaxel (Taxotere)-based chemotherapy has been proven to improve survival in this setting, a wide range of therapies may be effective for any individual. Palliative maneuvers, such as external-beam radiation, bisphosphonate therapy, radiopharmaceuticals, and pain management are critical for appropriate patient management. Several promising novel therapies are in late-stage testing and will hopefully provide more treatment options for these patients.
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PMID:Hormone-refractory prostate cancer: choosing the appropriate treatment option. 1739 82


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